Controlled delivery of intermittent stress augmentation pacing for cardioprotective effect

ABSTRACT

A device and method for delivering electrical stimulation to the heart in a manner which provides a protective effect against subsequent ischemia is disclosed. The protective effect is produced by configuring a cardiac pacing device to intermittently switch from a normal operating mode to a stress augmentation mode in which the spatial pattern of depolarization is varied to thereby subject a particular region or regions of the ventricular myocardium to increased mechanical stress.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. application Ser. No.12/109,169, filed Apr. 24, 2008, now issued as U.S. Pat. No. 8,027,723,which is a continuation of U.S. application Ser. No. 11/151,015, filedJun. 13, 2005, now issued as U.S. Pat. No. 7,366,568, the specificationsof which are herein incorporated by reference.

This application claims the benefit of U.S. Provisional Application No.60/678,338, filed on May 6, 2005, under 35 U.S.C. §119(e), which ishereby incorporated by reference.

This application is also related to U.S. Pat. No. 7,295,875, filed onJan. 6, 2005, entitled “INTERMITTENT STRESS AUGMENTATION PACING FORCARDIOPROTECTIVE EFFECT”, the disclosure of which is hereby incorporatedby reference.

FIELD OF THE INVENTION

This invention pertains to apparatus and methods for the treatment ofheart disease and to devices providing electrostimulation to the heartsuch as cardiac pacemakers.

BACKGROUND

Coronary artery disease (CAD) occurs when the coronary arteries thatsupply blood to the heart muscle become hardened and narrowed due toatherosclerosis. The arteries harden and become narrow due to thebuildup of plaque on the inner walls or lining of the arteries. Bloodflow to the heart is reduced as plaque narrows the coronary arteries.This decreases the oxygen supply to the heart muscle. CAD is the mostcommon type of heart disease, which is the leading cause of death in theU.S. in both men and women.

An atherosclerotic plaque is the site of an inflammatory reaction withinthe wall of an artery and is made up of a core containing lipid andinflammatory cells surrounded by a connective tissue capsule. Amyocardial infarction (MI), or heart attack, occurs when atheroscleroticplaque within a coronary artery ruptures and leads to the clotting ofblood (thrombosis) within the artery by exposing the highly thrombogeniclipid core of the plaque to the blood. The complete or nearly completeobstruction to coronary blood flow can damage a substantial area ofheart tissue and cause sudden death, usually due to an abnormal heartrhythm that prevents effective pumping.

Besides causing an MI, CAD can also produce lesser degrees of cardiacischemia due to the narrowing of a coronary artery lumen byatherosclerotic plaque. When blood flow and oxygen supply to the heartis reduced, patients often experience chest pain or discomfort, referredto as angina pectoris. Angina pectoris serves as a useful warning ofinsufficient myocardial perfusion which can lead to the more serioussituation such as a heart attack or cardiac arrhythmia. Patients whoexperience anginal episodes are commonly treated either with medicationor by surgical revascularization. It has also been found, however, thatpatients who experience anginal episodes prior to a heart attack oftenhave a lower mortality rate than heart attack patients who do notexperience such episodes. It is theorized that this phenomenon may bedue to ischemic preconditioning of the heart by the anginal episodeswhich thereby renders the myocardial tissue less likely to becomeinfarcted if blood supply is sharply reduced by a subsequent coronarythrombus.

SUMMARY

A device and method for delivering electrical stimulation to the heartin a manner which provides a protective effect against subsequentischemia is disclosed. The protective effect is produced by configuringa cardiac pacing device to intermittently switch from a normal operatingmode to a stress augmentation mode in which the spatial pattern ofdepolarization is varied to thereby subject a particular region orregions of the ventricular myocardium to increased mechanical stress.Techniques are also described for delivering the stress augmentationpacing at optimal times based upon, e.g., actual time of day,indications of posture change, and changes in autonomic balance.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an exemplary cardiac rhythm managementdevice for practicing the present invention.

FIGS. 2 through 4 illustrate exemplary algorithms for controllablyimplementing intermittent stress augmentation pacing.

DETAILED DESCRIPTION

The present disclosure relates to a method and device which employspacing therapy to precondition the heart to be less vulnerable to suddenreductions in blood flow. It has been found that intermittent pacing ofthe heart results in a cardioprotective effect which renders themyocardium more resistant (i.e., less likely to become infarcted) duringa subsequent episode of myocardial ischemia. As explained below, pacingtherapy may be applied in such a manner that certain regions of theventricular myocardium are subjected to an increased mechanical stress.It is believed that the increased myocardial stress preconditions theheart to better withstand the effects of subsequent ischemia through asignal transduction cascade which causes the release of certain cellularconstituents and/or induces expression of particular genes. Themechanism responsible for the cardioprotective effect of increasedstress may or may not be similar to the mechanism by which priorischemia preconditions the heart. It has been experimentally observed inanimal studies, however, that pacing therapy causing increased stress toa particular region of the myocardium can produce a cardioprotectiveeffect without making the region ischemic.

Described below is an exemplary device for delivering pacing therapy ina manner which preconditions the heart to better withstand subsequentischemia, referred to herein as intermittent stress augmentation pacing.Also set forth is an explanation as to how pacing may produce increasedmechanical stress to a myocardial region and an exemplary pacingalgorithm.

1. Mechanical Effects of Pacing Therapy

The degree of tension or stress on a heart muscle fiber as it contractsis termed the afterload. Because pressure within the ventricles risesrapidly from a diastolic to a systolic value as blood is pumped out intothe aorta and pulmonary arteries, the part of the ventricle that firstcontracts does so against a lower afterload than does a part of theventricle contracting later. The degree to which a heart muscle fiber isstretched before it contracts is termed the preload. The maximum tensionand velocity of shortening of a muscle fiber increases with increasingpreload, and the increase in contractile response of the heart withincreasing preload is known as the Frank-Starling principle. When amyocardial region contracts late relative to other regions, the earliercontraction of opposing regions stretches the later contracting regionand increases its preload. Thus, a myocardial region which contractslater than other regions during systole is subjected to both anincreased preload and an increased afterload, both of which cause theregion to experience increased wall stress.

When the ventricles are stimulated to contract by a pacing pulse appliedthrough an electrode located at a particular pacing site, the excitationspreads from the pacing site by conduction through the myocardium. Thisis different from the normal physiological situation, where the spreadof excitation to the ventricles from the AV node makes use of theheart's specialized conduction system made up of Purkinje fibers whichallows a rapid and synchronous excitation of the entire ventricularmyocardium. The excitation resulting from a pacing pulse applied to asingle site, on the other hand, produces a relatively asynchronouscontraction owing to the slower velocity at which excitation isconducted through the myocardium. Regions of the myocardium located moredistally from the pacing site are excited later than regions proximal tothe pacing site and, for the reasons explained above, subjected toincreased mechanical stress.

The ventricular contractions resulting from pacing pulses are thusgenerally not as synchronized as intrinsic contractions and maytherefore be hemodynamically less efficient. For example, inconventional bradycardia pacing, the pacing site is located in the rightventricle so that excitation must spread from the right ventricularpacing site through the rest the myocardium. The left ventricularcontraction then occurs in a less coordinated fashion than in the normalphysiological situation which can reduce cardiac output. This problemcan be overcome by pacing the left ventricle, either in addition to orinstead of the right ventricle, to produce a more coordinatedventricular contraction, referred to as cardiac resynchronizationpacing. Resynchronization pacing, besides overcoming the desynchronizingeffects of conventional pacing therapy, may also be applied to patientswho suffer from intrinsic ventricular conduction deficits in order toimprove the efficiency of ventricular contractions and increase cardiacoutput. Ventricular resynchronization therapy may be delivered as leftventricle-only pacing, biventricular pacing, or pacing delivered tomultiple sites in either or both ventricles.

In contradistinction to resynchronization therapy, pacing therapydelivered to produce a cardioprotective effect is pacing which isintended to produce a relatively asynchronous contraction so thatmyocardial regions located more distally from the pacing site aresubjected to increased mechanical stress. Such pacing, referred to asstress augmentation pacing, produces a pattern of myocardialdepolarization which is different from the dominant or chronicdepolarization pattern resulting from intrinsic or paced activation. Ifstress augmentation pacing is delivered on a relatively constant basis,however, the later contracting ventricular regions can undergohypertrophy and other remodeling processes in response to the increasedstress, and such remodeling can counteract the cardioprotective effects.The effectiveness of stress augmentation pacing is therefore increasedif such pacing is delivered as a single treatment or multiple treatmentsspread over some period of time so that remodeling does not occur.Stress augmentation pacing may be delivered by a variety of means. Inone embodiment, an external pacing device delivers pacing pulses to theheart via pacing electrodes which are incorporated into a catheter whichmay be disposed near the heart. Such a catheter may be one which is alsoused for other types of cardiac treatment or diagnosis such asangiography or angioplasty. Stress augmentation pacing may also bedelivered by an implantable pacing device. As described below, a cardiacpacing device may be programmed to deliver pacing which stresses aparticular myocardial region on an intermittent basis. The device mayalso be configured to intermittently pace multiple pacing sites in orderto provide a cardioprotective effect to multiple myocardial regions.

2. Exemplary Cardiac Device

Cardiac rhythm management devices such as pacemakers are usuallyimplanted subcutaneously on a patient's chest and have leads threadedintravenously into the heart to connect the device to electrodes usedfor sensing and pacing. A programmable electronic controller causes thepacing pulses to be output in response to lapsed time intervals andsensed electrical activity (i.e., intrinsic heart beats not as a resultof a pacing pulse). Pacemakers sense intrinsic cardiac electricalactivity by means of internal electrodes disposed near the chamber to besensed. A depolarization wave associated with an intrinsic contractionof the atria or ventricles that is detected by the pacemaker is referredto as an atrial sense or ventricular sense, respectively. In order tocause such a contraction in the absence of an intrinsic beat, a pacingpulse (either an atrial pace or a ventricular pace) with energy above acertain pacing threshold is delivered to the chamber.

FIG. 1 shows a system diagram of a microprocessor-based cardiac rhythmmanagement device or pacemaker suitable for practicing the presentinvention. The controller of the pacemaker is a microprocessor 10 whichcommunicates with a memory 12 via a bidirectional data bus. The memory12 typically comprises a ROM (read-only memory) for program storage anda RAM (random-access memory) for data storage. The controller could beimplemented by other types of logic circuitry (e.g., discrete componentsor programmable logic arrays) using a state machine type of design, buta microprocessor-based system is preferable. As used herein, the term“circuitry” should be taken to refer to either discrete logic circuitryor to the programming of a microprocessor.

The device is equipped with multiple electrodes each of which may beincorporated into a pacing and/or sensing channel. Shown in the figureare four exemplary sensing and pacing channels designated “a” through“d” comprising bipolar leads with ring electrodes 33 a-d and tipelectrodes 34 a-d, sensing amplifiers 31 a-d, pulse generators 32 a-d,and channel interfaces 30 a-d. Each channel thus includes a pacingchannel made up of the pulse generator connected to the electrode and asensing channel made up of the sense amplifier connected to theelectrode. By appropriate placement of the electrode, a channel may beconfigured to sense and/or pace a particular atrial or ventricular site.The channel interfaces 30 a-d communicate bidirectionally withmicroprocessor 10, and each interface may include analog-to-digitalconverters for digitizing sensing signal inputs from the sensingamplifiers and registers that can be written to by the microprocessor inorder to output pacing pulses, change the pacing pulse amplitude, andadjust the gain and threshold values for the sensing amplifiers. Thesensing circuitry of the pacemaker detects a chamber sense, either anatrial sense or ventricular sense, when an electrogram signal (i.e., avoltage sensed by an electrode representing cardiac electrical activity)generated by a particular channel exceeds a specified detectionthreshold. Pacing algorithms used in particular pacing modes employ suchsenses to trigger or inhibit pacing, and the intrinsic atrial and/orventricular rates can be detected by measuring the time intervalsbetween atrial and ventricular senses, respectively.

The electrodes of each bipolar lead are connected via conductors withinthe lead to a MOS switching network 70 controlled by the microprocessor.The switching network is used to switch the electrodes to the input of asense amplifier in order to detect intrinsic cardiac activity and to theoutput of a pulse generator in order to deliver a pacing pulse. Theswitching network also enables the device to sense or pace either in abipolar mode using both the ring and tip electrodes of a lead or in aunipolar mode using only one of the electrodes of the lead with thedevice housing or can 60 serving as a ground electrode. As explainedbelow, one way in which the device may alter the spatial distribution ofpacing is to switch from unipolar to bipolar pacing (or vice-versa) orto interchange which electrodes of a bipolar lead are the cathode andanode during bipolar pacing. A shock pulse generator 50 is alsointerfaced to the controller for delivering a defibrillation shock via apair of shock electrodes 51 to the atria or ventricles upon detection ofa shockable tachyarrhythmia.

The controller controls the overall operation of the device inaccordance with programmed instructions stored in memory, includingcontrolling the delivery of paces via the pacing channels, interpretingsense signals received from the sensing channels, and implementingtimers for defining escape intervals, sensory refractory periods, andother specified time intervals. An exertion level sensor 330 (e.g., anaccelerometer, a minute ventilation sensor, or other sensor thatmeasures a parameter related to metabolic demand) enables the controllerto adapt the pacing rate in accordance with changes in the patient'sphysical activity. A posture sensor may also be interfaced to thecontroller for determining the patient's posture when the heart rate andactivity level is measured. In one embodiment, the accelerometer 330 isa multi-axis accelerometer which allows the controller to compute thepatient's posture from measured accelerations along the multiple axes.

A telemetry interface 40 is also provided which enables the controllerto communicate with an external device 300 such as an externalprogrammer via a wireless telemetry link. An external programmer is acomputerized device with an associated display and input means that caninterrogate the pacemaker and receive stored data as well as directlyadjust the operating parameters of the pacemaker. The external device300 shown in the figure may also be a remote monitoring unit. Theexternal device 300 may also be interfaced to a patient managementnetwork 91 enabling the implantable device to transmit data and alarmmessages to clinical personnel over the network as well as be programmedremotely. The network connection between the external device 300 and thepatient management network 91 may be implemented by, for example, aninternet connection, over a phone line, or via a cellular wireless link.

The controller is capable of operating the device in a number ofprogrammed pacing modes which define how pulses are output in responseto sensed events and expiration of time intervals. Most pacemakers fortreating bradycardia are programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse. Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity such that a pacing pulse isdelivered to a heart chamber during a cardiac cycle only afterexpiration of a defined escape interval during which no intrinsic beatby the chamber is detected. Escape intervals for ventricular pacing canbe restarted by ventricular or atrial events, the latter allowing thepacing to track intrinsic atrial beats. Multiple excitatory stimulationpulses can be delivered to multiple sites during a cardiac cycle inorder to both pace the heart in accordance with a bradycardia mode andprovide additional excitation to selected sites.

3. Delivery of Intermittent Stress Augmentation Pacing

The device shown in FIG. 1 can be configured to deliver intermittentstress augmentation pacing in a number of different ways. In oneembodiment, which may be suitable for patients who need neitherbradycardia nor resynchronization pacing, the device is programmed todeliver no pacing therapy at all except at periodic intervals (e.g., forfive minutes each day). The pacing therapy may then be delivered in anyselected pacing mode such as right ventricle-only, left ventricle-only,or biventricular pacing. In certain patients who are implanted with apacemaker, intermittent pacing may occur fortuitously if the patient isrelatively chronotropically competent and without AV block and if theprogrammed escape intervals of the pacemaker are long enough. In orderto reliably provide augmented stress pacing and a cardioprotectiveeffect, however, the pacemaker should be programmed so that the pacingis delivered irrespective of the patient's intrinsic rate at scheduledintervals. Other embodiments, which may be suitable for patients whoneed bradycardia and/or resynchronization pacing, deliver intermittentstress augmentation pacing by intermittently varying the spatialdistribution of the pacing pulses applied by intermittently switchingfrom a normal operating mode to one or more stress augmentation pacingmodes. Switching to a stress augmentation mode may include altering thedevice's pacing pulse output configuration and/or pulse output sequencein order to initially excite different myocardial regions and therebycause later excitation of different regions distal to the pacing site orsites, where the pulse output configuration specifies a specific subsetof the available electrodes to be used for delivering pacing pulses andthe pulse output sequence specifies the timing relations between thepulses. The pulse output configuration is defined by the controllerselecting particular pacing channels for use in outputting pacing pulsesand by selecting particular electrodes for use by the channel withswitch matrix 70. If the normal operating mode is a primary pacing modefor delivering ventricular pacing therapy, the stress augmentation modemay then excite the ventricular myocardium at a site or sites differentfrom the primary pacing mode in order to vary the spatial pattern ofdepolarization and cause a particular myocardial region to experienceincreased mechanical stress. Intermittent spatial variation in pacingmay be produced, for example, by intermittently switching from a leftventricle-only pacing mode to a right ventricle-only pacing mode orvice-versa, intermittently switching from a biventricular or othermultiple ventricular pacing mode to a single ventricle pacing mode orvice-versa. Spatial variation in pacing may also be produced byemploying a bipolar pacing lead with electrodes spaced relatively farapart and then intermittently switching from unipolar to bipolar pacingor vice-versa, or intermittently interchanging which electrodes of thebipolar lead are the cathode and anode during bipolar pacing.

By the use of multiple pacing electrodes located at different pacingsites, a number of stress augmentation modes may be intermittentlyswitched to in order to provide augmented stress to multiple myocardialregions. Each such stress augmentation mode may be defined by a certainpulse output configuration and pulse output sequence, and delivery ofintermittent stress augmentation may involve temporarily switching toeach mode according to a programmed schedule, where the device remainsin the stress augmentation mode for a specified time period, referred toas the stress augmentation period (e.g., 5 minutes). By appropriateplacement of the pacing electrodes, a cardioprotective effect may beprovided to a large area of the ventricular myocardium. Such multiplepacing sites may be provided by multiple leads or by leads havingmultiple electrodes incorporated therein. For example, amultiple-electrode lead may be threaded into the coronary sinus in orderto provide multiple left ventricular pacing sites. In one embodiment,stress augmentation pacing is delivered during each cardiac cycle asmulti-site pacing through a plurality of the multiple electrodes. Inanother embodiment, the stress augmentation pacing is delivered assingle-site pacing where the pacing site may be alternated between themultiple electrodes during successive cardiac cycles or during differentstress augmentation periods. A switch to a stress augmentation mode mayalso include adjusting one or more pacing parameters such as the escapeintervals that determine pacing rate in order to ensure that the stressaugmentation paces are not inhibited by intrinsic cardiac activity.

As described above, the device controller may be programmed tointermittently switching from a normal operating mode to a stressaugmentation mode. In the normal operating mode, the device may eitherdeliver no therapy at all or may deliver a pacing therapy in a primarypacing mode with a different pacing configuration, a different pulseoutput sequence, and/or different pacing parameter settings from that ofthe stress augmentation mode. The device may be equipped with a singleventricular pacing channel or with multiple ventricular pacing channelseach having a pacing electrode disposed at a different pacing site. Inone example, the stress augmentation mode then uses at least one pacingchannel not used in the primary pacing mode. The device initiates stressaugmentation pacing upon receiving a command to switch to the stressaugmentation mode for a specified period of time, where such a commandmay be generated internally according to a defined schedule, receivedfrom an external programmer, or received via a patient managementnetwork. Once the command is received, the device may then simply switchto the stress augmentation mode for a specified period of time where thepacing parameters are predefined values. For example, the stressaugmentation pacing may be delivered to the ventricles in an atrialtriggered synchronous mode (e.g., DDD or VDD) with predefinedatrio-ventricular (AV) and ventricular-ventricular (VV) escape intervalsor in a non-atrial triggered ventricular pacing mode (e.g., VVI) with apre-defined VV escape interval where the length of the escape intervalsmay be set to values which result in a high pacing frequency. It may bedesirable, however, to incorporate additional steps into the algorithmbefore switching. For example, the escape intervals for the stressaugmentation mode may be dynamically determined before the mode switchin order to ensure a high pacing frequency. In an embodiment where thestress augmentation mode is a non-atrial triggered pacing mode, thedevice may measure the patient's intrinsic heart rate before the modeswitch and then set the VV escape interval so that the pacing rate forthe stress augmentation mode is slightly higher than the intrinsic rate.If the patient is receiving rate-adaptive ventricular pacing therapy inthe primary pacing mode, the VV escape interval for the stressaugmentation mode may be similarly modulated by an exertion levelmeasurement. In an embodiment where the stress augmentation pacing isdelivered in an atrial triggered pacing mode, the device may measure thepatient's intrinsic AV interval before the mode switch (e.g., as anaverage over a number of cycles preceding the mode switch) so that theAV escape interval for delivering ventricular pacing can be set to pacethe ventricles at a high frequency during the stress augmentation periodIt may also be desirable in certain patients for the device to check thepatient's exertion level before switching to the stress augmentationmode and cancel the mode switch if the exertion level is above a certainthreshold. This may be the case if the patient's ventricular function issomewhat compromised by the stress augmentation pacing. The device mayalso measure the patient's intrinsic AV interval before the mode switch(e.g., as an average over a number of cycles preceding the mode switch)so that the AV escape interval for delivering ventricular pacing in anatrial triggered mode can be set to pace the ventricles at a highfrequency during the stress augmentation period.

4. Controlled Delivery of Stress Augmentation Pacing

As explained above, stress augmentation pacing exerts itscardioprotective effect by causing mechanical asynchrony in the heart.The asynchrony causes increased cell stretch in the late contractingregion, and this may commence an intracellular signaling cascade whichtemporarily (hours to days) protects the heart (i.e. minimizes damage)from an ischemic event. Because at some of the cardioprotective effectis very short-term, the therapy would be optimally delivered when thepatient is most likely to have an ischemic event. It has been reportedthat there is circadian variation in the risk for having an MI.Specifically, patients are at highest risk in the morning, especiallyafter waking up from sleep. The implantable pacing device may beprogrammed to deliver therapy which is optimized with respect to thiscircadian variation by determining the time of day or when the patientawakes from sleep and delivering stress augmentation pacing accordingly.For example, the device could be programmed to deliver therapy at aspecific time of day from the time stamp in the device. Alternatively,the device could be configured to detect when the patient awakens byusing a posture sensor (such as a multi-axis accelerometer) to detect achange from a supine to a standing or sitting position. Awakening couldalso be detected by changes in heart rate variability (HRV) due to thesympathetic surge associated with waking up as assessed by either theLF/HF ratio, SDANN, or an autonomic balance monitor. Once awakening isdetected (or morning time is identified), the device may be programmedto initiate stress augmentation pacing (VDD or DDD, at a specific AVdelay and LV offset). As described above, the pacing could be deliveredfor a specified length of time (e.g. 5 minutes), then turned off forsome length of time, and started again where the amount of time thetherapy is delivered may be programmable or hard-coded into the device.The pacing site, AV delay, and LV offset may also be varied each timethe therapy is turned on in order to provide greater variation inmechanical contraction and hence greater stress augmentation. Also,depending on the degree of change in either posture or HRV, differentparameter settings of single or multiple pacing sites, AV delay, and LVoffset may also be used.

FIG. 2 illustrates an exemplary algorithm for delivering stressaugmentation pacing on a periodic basis scheduled in accordance with thepatient's expected waking up time. At step A1, the device waits for atimer expiration to switch to the stress augmentation mode, where thetimer is defined with an expiration which coincides with when thepatient is expected to awaken from sleep. Upon timer expiration, thedevice sets the AV delay and VV escape intervals for stress augmentationpacing in an atrial triggered pacing mode at step A2, where the escapeintervals may be set in accordance with the patient's currently measuredheart rate or intrinsic AV interval, set to pre-programmed fixed values,or set to values which vary each time the stress augmentation pacing isdelivered. At step A3, the device then switches to the stressaugmentation mode for a specified period of time. Upon expiration of thespecified time for delivery of the stress augmentation pacing at stepA4, the device ceases stress augmentation pacing at step A5 and returnsto step A1 to wait for another timer expiration.

Delivering stress augmentation pacing on a strictly time-scheduledbasis, however, presupposes that the patient wakes up at the same timeeach day. FIG. 3 illustrates another exemplary algorithm for deliveringstress augmentation pacing in accordance with signals received from aposture sensor which indicate when the patient is changing from a supineto erect or sitting position and is likely awakening from sleep. Ofcourse, a patient could lie down and get up at other times of the day.Therefore, in order to add greater specificity to the technique, a timermay optionally also be used to define a wakeup window so that the stressaugmentation pacing is only delivered when the patient changes from asupine to erect position during the wakeup window. For example, thewakeup window could be defined as being between 6:00 AM and 8:00 AM toallow for the fact that the patient may not get up at the same time eachday. When the posture sensor signals indicate the patient is rising fromsupine to an erect position during the wakeup window, it is very likelythat the patient is awakening from sleep which, as explained above, isan optimal time to deliver stress augmentation pacing. At step B1, thedevice waits for a signal from the posture sensor which indicates thatthe patient is rising from a supine position. At step B2, the devicechecks if the time of day is within the defined wakeup window. If so,the device sets the AV delay and VV escape intervals for stressaugmentation pacing as described above at step B3. At step B4, thedevice then switches to the stress augmentation mode for a specifiedperiod of time. Upon expiration of the specified time for delivery ofthe stress augmentation pacing at step B5, the device ceases stressaugmentation pacing at step B6 returns to step B1 to wait for anotherposture change.

Another surrogate indicator for a patient's awakening is a change inautonomic balance as can be determined by analyzing heart ratevariability. An increase in the activity of the sympathetic nervoussystem occurs upon awakening and could therefore be used by itself or incombination with the other techniques described above to indicate thatthe patient is awakening from sleep so that stress augmentation pacingcan be delivered at an optimal time. Also, an increase in sympatheticactivity, whether or not associated with awakening, may be indicative ofmetabolic stress and could therefore constitute a criterion for optimaldelivery of stress augmentation pacing. One means by which increasedsympathetic activity may be detected is via spectral analysis of heartrate variability. Heart rate variability refers to the variability ofthe time intervals between successive heart beats during a sinus rhythmand is primarily due to the interaction between the sympathetic andparasympathetic arms of the autonomic nervous system. Spectral analysisof heart rate variability involves decomposing a signal representingsuccessive beat-to-beat intervals into separate components representingthe amplitude of the signal at different oscillation frequencies. It hasbeen found that the amount of signal power in a low frequency (LF) bandranging from 0.04 to 0.15 Hz is influenced by the levels of activity ofboth the sympathetic and parasympathetic nervous systems, while theamount of signal power in a high frequency band (HF) ranging from 0.15to 0.40 Hz is primarily a function of parasympathetic activity. Theratio of the signal powers, designated as the LF/HF ratio, is thus agood indicator of the state of autonomic balance, with a high LF/HFratio indicating increased sympathetic activity. An LF/HF ratio whichexceeds a specified threshold value may be taken as an indicator thatcardiac function is not adequate. A cardiac rhythm management device canbe programmed to determine the LF/HF ratio by analyzing data receivedfrom its atrial or ventricular sensing channels. The intervals betweensuccessive atrial or ventricular senses, referred to as beat-to-beat orBB intervals, can be measured and collected for a period of time or aspecified number of beats. The resulting series of RR interval values isthen stored as a discrete signal and analyzed to determine its energiesin the high and low frequency bands as described above. Techniques forestimating the LF/HF ratio based upon interval data are described incommonly assigned U.S. patent application Ser. Nos. 10/436,876, filedMay 12, 2003, now issued as U.S. Pat. No. 7,069,070, entitled“STATISTICAL METHOD FOR ASSESSING AUTONOMIC BALANCE” and Ser. No.10/669,170, filed Sep. 23, 2003, now issued as U.S. Pat. No. 7,392,084,entitled “DEMAND-BASED CARDIAC FUNCTION THERAPY”, the disclosures ofwhich are hereby incorporated by reference.

FIG. 4 illustrates an exemplary algorithm for delivering stressaugmentation pacing on in accordance with an assessment of autonomicbalance. At step C1, the device waits until the LF/HF ratio asdetermined by analyzing data received from its atrial or ventricularsensing channels is above a specified threshold value. If so, the devicesets the AV delay and VV escape intervals for stress augmentation pacingas described above at step C2. At step C3, the device then switches tothe stress augmentation mode for a specified period of time. Uponexpiration of the specified time for delivery of the stress augmentationpacing at step C4, the device ceases stress augmentation pacing at stepC5 returns to step C1 to wait for another indication of increasedsympathetic activity.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Other such alternatives, variations, and modifications are intended tofall within the scope of the following appended claims.

What is claimed is:
 1. A cardiac rhythm management device, comprising: apulse generator for incorporation into a pacing channel for deliveringpacing pulses to a selected ventricular myocardial site; a controllerfor controlling the delivery of pacing pulses in accordance with aprogrammed pacing mode; wherein the controller is programmed to switchfrom a normal operating mode to a stress augmentation mode in which aparticular region or regions of the ventricular myocardium are subjectedto increased mechanical stress as compared with the stress experiencedby those regions during the normal operating mode; and, wherein thecontroller is programmed to switch to the stress augmentation mode uponexpiration of a timer and to cease operating in the stress augmentationmode upon expiration of a specified time period; and, wherein thecontroller is programmed to adjust one or more escape intervals whenswitching to the stress augmentation to increase the frequency ofpacing.
 2. The device of claim 1 wherein the normal operating mode is aprimary pacing mode for delivering ventricular pacing therapy andwherein stress augmentation mode causes a different depolarizationpattern than the primary pacing mode.
 3. The device of claim 2 whereinthe stress augmentation mode excites the ventricular myocardium at asite or sites different from the primary pacing mode.
 4. The device ofclaim 2 wherein the switch from a primary pacing mode to a stressaugmentation mode involves switching form bipolar pacing to unipolarpacing or vice-versa.
 5. The device of claim 2 wherein the switch from aprimary pacing mode to a stress augmentation mode involves switchingwhich electrode of a bipolar pacing lead is the cathode and whichelectrode is the anode.
 6. The device of claim 2 wherein the controlleris further programmed to: deliver pacing pulses to a plurality ofventricular pacing sites; and, wherein the stress augmentation mode usesat least one pacing channel not used in the primary pacing mode.
 7. Adevice for operating a cardiac rhythm management device, comprising: apulse generator for incorporation into a pacing channel for deliveringpacing pulses to a selected ventricular myocardial site; a controllerfor controlling the delivery of pacing pulses in accordance with aprogrammed pacing mode; a sensor for sensing a patient's posture;wherein the controller is programmed to switch from a normal operatingmode to a stress augmentation mode in which a particular region orregions of the ventricular myocardium are subjected to increasedmechanical stress as compared with the stress experienced by thoseregions during the normal operating mode; and, wherein the controller isprogrammed to switch to the stress augmentation mode upon receiving asignal from the posture sensor indicating that the patient's posture haschanged from a supine position to an erect or sitting position and tocease operating in the stress augmentation mode upon expiration of aspecified time period.
 8. The device of claim 7 wherein the normaloperating mode is a primary pacing mode for delivering ventricularpacing therapy and wherein stress augmentation mode causes a differentdepolarization pattern than the primary pacing mode.
 9. The device ofclaim 8 wherein the stress augmentation mode excites the ventricularmyocardium at a site or sites different from the primary pacing mode.10. The device of claim 8 wherein the switch from a primary pacing modeto a stress augmentation mode involves switching form bipolar pacing tounipolar pacing or vice-versa.
 11. The device of claim 8 wherein theswitch from a primary pacing mode to a stress augmentation mode involvesswitching which electrode of a bipolar pacing lead is the cathode andwhich electrode is the anode.
 12. The device of claim 8 wherein thecontroller is further programmed to: deliver pacing pulses to aplurality of ventricular pacing sites; and, wherein the stressaugmentation mode uses at least one pacing channel not used in theprimary pacing mode.
 13. The device of claim 7 wherein the controller isfurther programmed to switch to the stress augmentation mode for aspecified time period upon receiving a signal from the posture sensorindicating that the patient's posture has changed from a supine positionto an erect or sitting position and if the time of day is within adefined wakeup window as determined by a time stamp.
 14. A device foroperating a cardiac rhythm management device, comprising: a pulsegenerator for incorporation into a pacing channel for delivering pacingpulses to a selected ventricular myocardial site; a sensing amplifierfor incorporation into a sensing channel for detecting cardiac activity;a controller for controlling the delivery of pacing pulses in accordancewith a programmed pacing mode; wherein the controller is programmed todetermine an LF/HF ratio by analyzing data received from the sensingchannel; wherein the controller is programmed to switch from a normaloperating mode to a stress augmentation mode in which a particularregion or regions of the ventricular myocardium are subjected toincreased mechanical stress as compared with the stress experienced bythose regions during the normal operating mode; and, wherein thecontroller is programmed to switch to the stress augmentation mode whenthe LF/HF ratio is above a specified threshold value and to ceaseoperating in the stress augmentation mode upon expiration of a specifiedtime period.
 15. The device of claim 14 wherein the normal operatingmode is a primary pacing mode for delivering ventricular pacing therapyand wherein stress augmentation mode causes a different depolarizationpattern than the primary pacing mode.
 16. The device of claim 15 whereinthe stress augmentation mode excites the ventricular myocardium at asite or sites different from the primary pacing mode.
 17. The device ofclaim 15 wherein the switch from a primary pacing mode to a stressaugmentation mode involves switching form bipolar pacing to unipolarpacing or vice-versa.
 18. The device of claim 15 wherein the switch froma primary pacing mode to a stress augmentation mode involves switchingwhich electrode of a bipolar pacing lead is the cathode and whichelectrode is the anode.
 19. The device of claim 15 wherein thecontroller is further programmed to: deliver pacing pulses to aplurality of ventricular pacing sites; and, wherein the stressaugmentation mode uses at least one pacing channel not used in theprimary pacing mode.
 20. The device of claim 15 further comprising: asensor for measuring a patient's exertion level; and, wherein thecontroller is further programmed to cease operating in the stressaugmentation mode if the measured exertion level is above a specifiedthreshold.